The objective of the proposed studies is the elucidate the mechanism for the now well-documented role of complement in the pathogenesis of tissue injury in the ischemic myocardium. However to date, there are two most critical questions that have not been addressed and which, therefore, form the rationale for the proposed investigations. a. Does the complement-dependent injury of the ischemic myocardium occur directly as a result of complement activation? b. Alternatively or in addition, does the complement-dependent injury of the ischemic myocardium occur indirectly as a result of the production of phlogistic, complement-derived activation products which then mediate subsequent neutrophil-dependent myocardial tissue injury? Two Specific Aims will address both of these questions with the major objective and thrust directed towards elucidating the mechanisms underlying the role of complement in mediating tissue injury inthe ischemic myocardium. 1. Characterize temporally the activation and localization of various complement components (C3, C5 and C5b-9) within the ishcemic myocardium at various times after coronary artery occlusion. 2. Characterize the effectsof prior C3 and C5, C5 and/or neutrophil depletion upon the subsequent extent of myocardial tissue injury after coronary artery occlusion. A baboon model will be utilized because this non-human primate has a coronary circulation and complement system that is analogous to man. Therefore, the information gained in the proposed studies will closely approximate the role of complement in the pathogenesis of myocardial tissue injury in man after acute myocardial infarction and hopefully might lead to effective therapeutic interventions to decrease infarct size by abrogating complement-dependent injury of the ischemic myocardium.